Influence of Chitin Source and Polymorphism on Powder Compression and Compaction: Application in Drug Delivery.

The objective of the research reported herein is to compare the compaction properties of three different chitin extracts from the organisms most used in the seafood industry; namely crabs, shrimps and squids. The foregoing is examined in relation to their polymorphic forms as well as compression and compaction behavior. Chitin extracted from crabs and shrimps exhibits the α-polymorphic form whilst chitin extracted from squid pins displays a ß-polymorphic form. These polymorphs were characterized using FTIR, X-ray powder diffraction and scanning electron microscopy. Pore diameter and volume differ between the two polymorphic powder forms. The ß form is smaller in pore diameter and volume. Scanning electron microscopy of the two polymorphic forms shows clear variation in the arrangement of chitin layers such that the α form appears more condensed due to the anti-parallel arrangement of the polymer chains. True, bulk and tapped densities of these polymorphs and their mixtures indicated poor flowability. Nevertheless, compression and compaction properties obtained by applying Heckle and Kawakita analyses indicated that both polymorphs are able to be compacted with differences in the extent of compaction. Chitin compacts, regardless of their origin, showed a very high crushing strength with very fast dissolution which makes them suitable for use as fast mouth dissolving tablets. Moreover, when different chitin powders are granulated with two model drugs, i.e., metronidazole and spiramycin they yielded high crushing strength and their dissolution profiles were in accordance with compendial requirements. It is concluded that the source of chitin extraction is as important as the polymorphic form when compression and compaction of chitin powders is carried out.

Understanding the Performance of a Novel Direct Compression Excipient Comprising Roller Compacted Chitin.

Chitin has been investigated in the context of finding new excipients suitable for direct compression, when subjected to roller compaction. Ball milling was concurrently carried out to compare effects from different energy or stress-inducing techniques. Samples of chitin powders (raw, processed, dried and humidified) were compared for variations in morphology, X-ray diffraction patterns, densities, FT-IR, flowability, compressibility and compactibility. Results confirmed the suitability of roller compaction to convert the fluffy powder of raw chitin to a bulky material with improved flow. X-ray powder diffraction studies showed that, in contrast to the high decrease in crystallinity upon ball milling, roller compaction manifested a slight deformation in the crystal lattice. Moreover, the new excipient showed high resistance to compression, due to the high compactibility of the granules formed. This was correlated to the significant extent of plastic deformation compared to the raw and ball milled forms of chitin. On the other hand, drying and humidification of raw and processed materials presented no added value to the compressibility and compactibility of the directly compressed excipient. Finally, compacted chitin showed direct compression similarity with microcrystalline cellulose when formulated with metronidazole (200 mg) without affecting the immediate drug release action of the drug.

A Direct Compression Matrix Made from Xanthan Gum and Low Molecular Weight Chitosan Designed to Improve Compressibility in Controlled Release Tablets.

The subject of our research is the optimization of direct compression (DC), controlled release drug matrices comprising chitosan/xanthan gum. The foregoing is considered from two main perspectives; the use of low molecular weight chitosan (LCS) with xanthan gum (XG) and the determination of important attributes for direct compression of the mixtures of the two polymers. Powder flow, deformation behaviour, and work of compression parameters were used to characterize powder and tableting properties. Compression pressure and LCS content within the matrix were investigated for their influence on the crushing strength of the tablets produced. Response surface methodology (RSM) was applied to determine the optimum parameters required for DC of the matrices investigated. Results confirm the positive contribution of LCS in enhancing powder compressibility and crushing strength of the resultant compacts. Compactibility of the XG/LCS mixtures was found to be more sensitive to applied compression pressure than LCS content. LCS can be added at concentrations as low as 15% w/w to achieve hard compacts, as indicated by the RSM results. The introduction of the plasticity factor, using LCS, to the fragmenting material XG was the main reason for the high volume reduction and reduced porosity of the polymer mixture. Combinations of XG with other commonly utilized polymers in controlled release studies such as glucosamine, hydroxypropyl methylcellulose (HPMC), Na alginate (ALG), guar gum, lactose and high molecular weight (HMW) chitosan were also used; all the foregoing polymers failed to reduce the matrix porosity beyond a certain compression pressure. Application of the LCS/XG mixture, at its optimum composition, for the controlled release of two model drugs (metoprolol succinate and dyphylline) was examined. The XG/LCS matrix at 15% w/w LCS content was found to control the release of metoprolol succinate and dyphylline. The former preparation confirmed the strong influence of compression pressure on changing the drug release profile. The latter preparation showed the ability of XG/LCS to extend the drug release at a fixed rate for 12 h of dissolution time after which the release became slightly slower.

Modification of α-lactose monohydrate as a direct compression excipient using roller compaction.

Roller compaction was used to prepare a direct-compressed lactose excipient using crystalline α-lactose monohydrate. The effect of various roller compaction process parameters (compaction pressure, compaction repetition, and speed ratio) on the characteristics of compacted α-lactose monohydrate was investigated. Results were compared with data obtained using industrial spray-dried lactose and lactose samples with different degrees of crystallinity. XRPD analysis revealed that roller compaction reduced the crystallinity of α-lactose monohydrate, and the resulting material is similar to spray-dried lactose in behavior as a direct compression excipient. Roller compaction introduced desirable characteristics to the raw α-lactose monohydrate by inducing changes in crystallinity and particle morphology. Scanning electron microscopy results indicated that the compaction process converted some of the original torpedo-shaped crystals of α-lactose monohydrate into a more cylindrical shape with rounded edges. Compaction pressure and repetition of compaction have a significant effect on the modification of the crystallinity of the processed, raw α-lactose monohydrate.